crossing96/oncoscreening huggingface dataset:
Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides.	The major goal of epigenetic therapy is to reverse aberrant promoter hypermethylation and restore normal function of tumor suppressor genes by the use of chromatin-modifying drugs. Decitabine, or 5-aza-2'-deoxycytidine (5-aza-CdR), is a well-characterized drug that is now Food and Drug Administration approved for the treatment of myelodysplastic syndrome. Although 5-aza-CdR is an extremely potent inhibitor of DNA methylation, it is subject to degradation by hydrolytic cleavage and deamination by cytidine deaminase. We show that short oligonucleotides containing a 5-aza-CdR can also inhibit DNA methylation in cancer cells at concentrations comparable with 5-aza-CdR. Detailed studies with S110, a dinucleotide, showed that it works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. Stability of the triazine ring in aqueous solution was not improved in the S110 dinucleotide; however, deamination by cytidine deaminase was dramatically decreased. This is the first demonstration of the use of short oligonucleotides to provide effective delivery and cellular uptake of a nucleotide drug and protection from enzymatic degradation. This approach may pave the way for more stable and potent inhibitors of DNA methylation as well as provide means for improving existing therapeutics.	bladder
Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo.	PURPOSE: External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. MATERIALS AND METHODS: We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. RESULTS: IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p = 0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p = 0.04). CONCLUSIONS: Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial.	bladder
Thirty years of BCG immunotherapy for non-muscle invasive bladder cancer: a success story with room for improvement.	Over the last three decades, intravesical immunotherapy with the biological response modifier Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been established as the most effective adjuvant treatment for preventing local recurrences and tumor progression following transurethral resection of non-muscle invasive bladder cancer. A large number of clinical trials have established a major role for BCG immunotherapy in urological oncology. In parallel, the major principles of the immunological mechanism have been revealed. In spite of this success, questions still remain regarding its clinical use, mechanism of action and potential improvement. This review provides a comprehensive insight into the historical era of BCG immunotherapy, the current indications for clinical application, the complex mechanism of action and possible future developments.	bladder
Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents.	Recently, we reported prognostic significance of thromboxane synthase (TXAS) gene expression in invasive bladder cancer. The positive correlation between elevated TXAS expression and shorter patient survival supports a potential role for TXAS-regulated pathways in tumor metastases. In this study, using immunohistochemical analysis, we found an increased expression of TXAS protein in bladder cancer. Treatment of T24 and transitional cell carcinoma TCC-SUP bladder cancer cells with the TXAS inhibitors furegrelate or ozagrel induced an apoptotic effect measured as an increase in caspase-3 activation and cell death, and decreased survivin expression. Pharmacological inhibition of TXAS using the TXAS inhibitor furegrelate increased sensitivity to the chemotherapeutic agents cisplatin and paclitaxel. Molecular inhibition of TXAS expression by siRNA significantly decreased cell growth and migration. In concordance with the pharmacological data, siRNA-mediated reduction of TXAS expression increased sensitivity to cisplatin and paclitaxel in T24 and TCC-SUP cells. In summary, the data support a role for the thromboxane A(2) pathway in the pathogenesis of bladder cancer and the potential utility of modulation of this signaling pathway for cancer chemotherapy.	bladder
Prognostic index for primary adenocarcinoma of the urinary bladder.	AIM: To determine the working independent prognostic factors and the prognostic index of adenocarcinoma of the urinary bladder. The effect of adding postoperative radiotherapy to radical cystectomy on this prognostic index was also investigated. PATIENTS AND METHODS: Two hundred and sixteen patients having adenocarcinoma of the urinary bladder were treated with radical cystectomy and pelvic lymphadenectomy with (82 patients) or without (134) postoperative radiotherapy. Postoperative radiotherapy (PORT) was given to the whole pelvis in a dose of 50 Gy/25 fractions over 5 weeks, and started 4-10 weeks after surgery. RESULTS: The 5-year disease-free survival rate was 44 +/- 4% for the whole group. Postoperative radiotherapy improved the disease-free survival significantly from 33 +/- 6% for cystectomy alone Introduction to 58 +/- 6% for PORT patients (P = 0.002). The independent prognostic factors for DFS were the pathological stage, histological subtypes, nodal involvement and the addition of postoperative radiotherapy. The stratification of patients using prognostic indices according to the pathological findings produces identifiable prognostic groups. Postoperative radiotherapy improved the DFS significantly in the intermediate and high risk indices (p = 0.0004 and 0.0002 respectively). CONCLUSIONS: The identified prognostic indices with their prognostic group could be used not only as a predictor of disease-free survival but also as a good predictor for the need to add adjuvant therapy in adenocarcinoma of the urinary bladder.	bladder
[Infiltrating bladder tumours].	Invasive bladder tumours are defined as carcinomas infiltrating the muscular fibbers of the bladder wall. The assessment of tumour extension includes a clinical examination and an abdominopelvic computed tomography. The gold standard therapy is cystectomy in women and radical cystoprostatectomy in men. In patients with in situ bladder cancers, this treatment results in a five-year specific survival of 90 percent. Adjuvant chemotherapy may be considered in patients with extravesical lesions or lymphatic extension. After bladder resection, several types of urinary diversion may be considered. Ileal neobladder reconstruction, when possible, should be preferred. Patients must be monitored twice a year during the first 3 years, then once a year, to screen for a possible local or remote recurrence. The efficiency of the neobladder should be monitored regularly to ensure a satisfactory urinary voiding as well as continence acquisition, which can be achieved through auto-rehabilitation. In case of recurrence, therapeutic options should be debated in multidisciplinary team meetings; chemotherapy with cisplatin or/and gemcitabine remains the main therapeutic weapon.	bladder
[Diagnosis and treatment of superficial bladder cancers].	By definition, superficial bladder tumours do not invade the bladder muscle. The two main risk factors are smoking and industrial carcinogens. Gross hematuria is the most common presenting sign of bladder tumour; its finding should always prompt a cystoscopy of the lower urinary tract. The finding of a bladder tumour always requires assessment of the upper urinary tract. Endoscopic resection, performed under locoregional or general anaesthesia, is the first step in treating superficial bladder tumours. It should be complete and as deep as possible (muscle). Additional treatment with intravesical instillations may be necessary according to the at-risk group defined by the Cancer Committee of the French Urological Association. Intravesical instillations essentially consist of intravesical chemotherapy (mitomycin C) and intravesical immunotherapy (BCG). They aim at reducing the risk of tumour recurrence, as well as the risk of progression to bladder muscle invasion.	bladder
Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human bladder cancer.	The idea of generating cytotoxic T-lymphocytes that have anti-tumor activity has been the focus of many clinical trials aimed at delivering effective immunotherapy to cancer patients. We have gained insight into the human immune system in cancer patients as a result of these numerous clinical investigations. It is now clear that although various vaccination methods are capable of inducing tumor antigen-specific T-cells in the circulating blood, these immunological responses are infrequently correlated with clinical responses. Therefore, it appears that priming of a T-cell response is not sufficient for tumor regression and other avenues, downstream of the priming phase, need to be investigated. Mechanisms of immune evasion at the effector phase of the anti-tumor phase are currently under investigation, with an increasing focus on the tumor microenvironment. There is evidence indicating that multiple variables may contribute to immune escape, including: regulatory cells; inhibitory ligands on tumor cells, such as PD-L1 and B7x; soluble factors such as TGF-beta and IL-10; and nutrient-catabolizing enzymes, such as indoleamine-2,3-dioxygenase (IDO). In addition, there are ongoing efforts to assess the presence and function of effector cells within the tumor microenvironment. Tumor infiltrating lymphocytes (TILs) have been observed in patients with melanoma, colon cancer, and ovarian cancer. TILs in these patients have been associated with favorable clinical outcomes. In the clinical setting of bladder cancer, as compared to melanoma, there is limited data regarding TILs. This review will focus on immunological responses to bladder cancer and ongoing studies to identify factors that are amenable to therapeutic manipulation.	bladder
Methylenetetrahydrofolate reductase and methionine synthase polymorphisms and risk of bladder cancer in a Tunisian population.	Folate insufficiency can induce carcinogenesis by decreasing DNA methylation. It is well known that DNA hypomethylation is a common feature in a number of cancers. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are enzymes that play central roles in the folate metabolic pathway. Two common polymorphisms in the MTHFR gene (C677T and A1298C) and one in the MS gene (A2756G) are associated with decreased enzymatic activity. In this work, we have conducted a case-control study to assess the role of these three polymorphisms in bladder cancer development in North Tunisia. For MS A2756G, gene and genotypic distributions differed significantly between cases and controls. Furthermore, individuals carrying at least one copy of the variant allele presented a 2.33 times increased risk of developing bladder cancer than their control group [P = 0.001, odds ratio (OR) = 2.33; 95% confidence interval (CI) 1.34-4.06]. Statistically significant odds ratios were also found in patients heterozygous for MTHFR A1298C, who have a 1.8-fold higher risk of developing bladder cancer (P = 0.03, OR = 1.86; CI 95% 1.04-3.33). While the isolated polymorphism C677T did not appear to influence bladder cancer susceptibility, results suggest that it might act with an additive contribution determined by variation at MTHFR A1298C. Identical cumulative effect was detected for the MTHFR A1298C and MS 2756 genotypes. Patients harboring at least one mutant allele for each of the three positions analyzed showed a 4.76-fold increased risk of developing bladder cancer in comparison to their reference group (P = 0.02, OR = 4.76; CI 95% 1.26-17.98).	bladder
Soft tissue tumors of the urinary bladder Part II: malignant neoplasms.	Most bladder tumors arise from the urothelium. However, there are several uncommon but significant malignant bladder lesions that must be differentiated from urothelial carcinomas and from benign lesions of the bladder. The second half of this two-part review will describe rare nonurothelial malignant tumors of the urinary bladder including leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, malignant fibrous histiocytoma (undifferentiated sarcoma), primitive neuroectodermal tumor, malignant peripheral nerve sheath tumor, hemangiopericytoma, and alveolar soft-parts sarcoma. Common clinical presentations, morphologic characteristics, and immunohistochemical features are described to aid the practicing pathologist in the identification of these entities. Because the distinction between malignant and benign lesions has significant therapeutic and prognostic implications, key factors for differentiating them are presented.	bladder
The influence of thermo-chemotherapy on bladder tumours: an immunohistochemical analysis.	To study the influence of microwave induced thermo-chemotherapy on high-grade urothelial cell carcinomas. Five groups of each three patients were formed of whom initial biopsies and cystectomy samples were collected. Patients were treated 2 days prior to cystectomy with mitomycin-C (group 1), hyperthermia (group 2) or thermo-chemotherapy (group 3). Group 4 patients had been treated with a cycle of six thermo-chemotherapy treatments prior to cystectomy and group 5 patients served as control (no treatment). Tumour samples were stained with Haematoxylin and Eosin, monoclonal antibody Ki-67 and the monoclonal antibody p53. In six out of the nine patients treated with hyperthermia a decrease in proliferation activity in the tumour was found. Seven out of nine patients treated with hyperthermia showed a decrease in p53 activity. A decrease in proliferation activity and p53 activity illustrate the potential role of thermo-chemotherapy as a promising intravesical treatment.	bladder
Multimodal perioperative plan for radical cystectomy and intestinal urinary diversion. I. Effect on recovery of intestinal function and occurrence of complications.	OBJECTIVES: To discuss a multimodal perioperative plan aimed at reducing postoperative ileus and complications associated with radical cystectomy and urinary reconstruction. METHODS: The protocol consisted of preoperative, intraoperative, and postoperative measures. The clinical parameters assessed were the time to the return of bowel movements, the presence and duration of postoperative ileus, the presence and duration of an intolerance to oral feeding, the interval to re-institution of a regular diet, and complications. The biochemical parameters (serum total protein and albumin levels and lymphocyte counts) were also assessed. A sample of 40 patients treated before the implementation of this protocol was included for comparison. RESULTS: A total of 71 patients, mean age 74 years and American Society of Anesthesiologists status 2 and 3, consecutively underwent radical surgery for bladder cancer and were evaluable for results and complications. Urinary diversion was a heterotopic neobladder in 27 patients (38%), orthotopic in 23 (32.3%), and an ileal conduit in 21 (29.5%). Bowel movements returned after a median of 2 days (range 1 to 6), intolerance to oral feeding was observed in 17 (23.9%) of 71 patients, and the median time to re-institution of a regular diet was 4 days (range 3 to 9). The complication rate was 26.7%, and the mortality rate was 4.2%. No effects were observed on postoperative protein depletion. In the historical group, the median time to diet resumption was 8 days (range 7 to 12). CONCLUSIONS: A short time to the resumption of normal intestinal function and a low incidence of postoperative ileus after cystectomy was observed. However, the incidence of postoperative protein depletion was unaffected. Additional studies should address this subject.	bladder
Do bladder cancer patients with metastatic spinal cord compression benefit from radiotherapy alone?	OBJECTIVES: To investigate the role of radiotherapy (RT) alone in metastatic spinal cord compression (MSCC) patients with bladder cancer. METHODS: Thirty-two MSSC patients with bladder cancer were included in this retrospective review. Potential prognostic factors were investigated for functional outcome, local control of MSCC, and survival: age, gender, performance status, visceral metastases at the time of RT, number of involved vertebrae, ambulatory status, time of developing motor deficits before RT, and radiation schedule (short-course RT [1 week or less] versus long-course RT [2 to 4 weeks]). RESULTS: Two patients (6%) showed improvement of motor function, 25 (78%) no change, and 5 (16%) deterioration. Better functional outcome was significantly associated with a better performance status (P = 0.035). A trend was observed for absence of visceral metastases (P = 0.054). Five patients developed a recurrence of MSCC in the preirradiated spinal region, which was treated with reirradiation (0 improvement, 4 no change, 1 deterioration). Median survival was 4 months. The 1-year survival rate was only 16%. Better survival was associated with absence of visceral metastases, being ambulatory, involvement of only one to three vertebrae, and better performance status. CONCLUSIONS: Improvement of motor function was rare. For patients not suitable for decompressive surgery, short-course RT seems preferable because it provides a functional outcome similar to that with long-course RT and is more patient convenient. If the patient's prognosis seems extremely poor in terms of functional outcome and survival, single-fraction RT or even best supportive care may be considered.	bladder
[Gene therapy of bladder cancer by using recombinant adeno-associated virus-endostatin: experiments in vitro and in vivo].	OBJECTIVE: To package recombinant adeno-associated virus-endostatin (rAAV-ES) and study its anti-tumor effect in vitro and in vivo. METHODS: rAAV-ES was packaged with co-transfection technique and transfected into the human bladder cancer cells of the line EJ. 24 h later ELISA was used to examine the concentration of ES in the supernatant. The inhibition of human umbilical veins endothelial cells (HUVECs) chemotactic movement were examined by Transwell system. Nude Balb/c mice were divided into 4 groups: (1) 5 mice were inoculated with the EJ cells transfected with rAAV-ES or rAAV-enhanced yellow fluorescence protein (rAAV-EYFP) for 3 days to the subcutaneous tissues of bilateral shoulders so as to observe the growth of tumor. (2) 24 mice were injected with rAAV-ES intramuscularly and then the serum ES was examined every 10 days since the 10 th day after the injection. (3) 36 mice were randomly subdivided into 3 equal subgroups to be injected with rAAV-ES, rAAV-EYFP, or RPMI medium, inoculated with EJ cells 2 weeks later, and then killed 50 days later to observe the size of tumor. (4) 4 healthy mice and 4 mice injected with rAAV-ES for 8 weeks were killed with their hearts and brains taken out to observe the side effects. RESULTS: rAAV-ES was packaged successfully. The ES concentration in the supernatant of culture fluid of the EJ cell transfected with rAAV-ES was 54.09 ng/ml. The inhibition rate of the HUVECs chemotactic movement was 37.45%. The xenograft formation rate was 2/5 for the EJ cells transfected with rAAV-ES. The serum ES levels of the mice injected with rAAV-ES remained high. The tumor size in the mice injected with rAAV-ES was significantly smaller than those of the other groups (both P < 0.01). No pathological changes was found in the hearts and brains in the mice injected with rAAV-ES. CONCLUSION: rAAV-ES inhibits tumor angiogenesis, and tumor formation and progression. Successful packaging of rAAV-ES has laid a foundation for gene therapy of bladder cancer.	bladder
[Identification of gene expression patterns in superficial and invasive human bladder cancers].	OBJECTIVE: To study the difference of gene expression patterns in invasive and superficial human bladder cancers. METHODS: cDNA microarray was used to detect the RNA in 12 samples of invasive and superficial human bladder cancers and 6 samples of normal bladder tissues as control group obtained during operation. Then, the scanogram was analyzed by applying the image processing software GenePix Pro 3.0 so as to obtain the relevant data of genes. Finally, we analyzed these data by some knowledge about the type of genes and the characteristic of human bladder cancer. RESULTS: There were 714 genes with remarkable differences in the samples of superficial bladder cancer, of which 480 were down-regulated and 234 were up-regulated; and there were 470 genes with remarkable differences in the samples of invasive bladder cancer, of which 302 were down-regulated and 168 were up-regulated. The number of down-regulated genes in the samples of superficial bladder cancer was two times that of up-regulated genes. Most of the up-regulated genes were metabolism, cell signal transduction, DNA combination and transcription, protein translation and synthesis, and development-related genes; and most of the down-regulated genes were immunization-related genes. The down-regulation of immune-related genes was more remarkable in the invasive bladder cancer than in the superficial tumor. CONCLUSION: There are many same features in gene expression spectrum in invasive and superficial human bladder cancers. However, the number of gene phenotype of the superficial human bladder cancer is more than that of invasive one. The loss of immunization-related genes is more severe in the invasive human bladder cancer than in the superficial tumor.	bladder